Mechanisms of pathogenesis in allergic asthma: role of interleukin-23

Asthma is a chronic airway inflammatory disease characterized by intense leukocyte and eosinophilic infiltration accompanied by mucus hypersecretion and tissue hyperresponsiveness. Recent evidence suggests that T-helper (Th)2 cells and their cytokine products orchestrate the pathology of asthma. In addition, Th17 cells are implicated in the pathogenesis of antigen-induced airway inflammation. The Th17 related cytokine interleukin (IL)-23 plays important roles in many immunological diseases, such as experimental autoimmune encephalomyelitis, rheumatoid arthritis, psoriasis and inflammatory bowel disease. Several reports describe the role of IL-23 in the pathogenesis of allergic asthma in both human and mice. IL-23 leads to neutrophil infiltration in the airway of asthmatic mice, which is characteristic of severe asthma resulting from Th17 development and subsequently IL-17 secretion. IL-23 can also promote eosinophil infiltration in the airway, which is a hallmark of allergic asthma. These studies suggest that IL-23 could be a promoting factor in the development of allergic asthma and likewise would be a target for asthma therapy. In support of this view, trials of anti-IL-23 therapy have been attempted in human and mouse asthma models with encouraging outcomes. This review presents the role of IL-23 in asthma according to recent clinical trials and animal model studies. The proposed mechanisms of IL-23-induced airway inflammation and the agents currently being tested that target IL-23 related pathways are discussed.